TABLE 2.
Direct and indirect antimicrobial effects of antipyretic drugsa
| Effect | Organism(s) tested and effect(s) (reference[s]) of indicated drug(s) |
|||||
|---|---|---|---|---|---|---|
| Acetaminophen | Concn (mg/ml) | Salicylic acid | Concn (mg/ml) | Other NSAIDs | Concn (mg/ml) | |
| Motility | Reduction of motility of Burkholderia cepacia (22), Escherichia coli (22, 23), Proteus mirabilis (22), Proteus vulgaris (22), Providencia rettgeri (22), Providencia stuartii | 0.69 (22), 0.18 (23) | ||||
| Blocking of flagellin production by Escherichia coli | 0.69 (22) | |||||
| Reduction in flagella production by Proteus mirabilis | 2.76 (22) | |||||
| No effect on motility of Pseudomonas aeruginosa | 0.69 (22) | |||||
| Adherence | Reduction of fimbriae production by Escherichia coli | 0.35 (25) | Reduction of adhesion of Escherichia coli to uroepithelial cells due to reduced fimbriae production and changes in surface hydrophobicity (ibuprofen) | 0.002 (9) | ||
| Reduction of hemagglutinin production by Escherichia coli | 1.38 (26) | Reduction of adherence of Escherichia coli to silastic catheters (ibuprofen) | 0.39 (27) | |||
| Reduction of fibronectin binding in Staphylococcus aureus | 0.03 (29) | Reduction of adhesion of Candida albicans, Candida glabrata and Candida krusei (ibuprofen) | 0.13 (16) | |||
| Reduction of adhesin production by Staphylococcus epidermidis | 0.69 (30) | Reduction of adherence of Pseudomonas aeruginosa, Haemophilus influenzae, Staphylococcus epidermidis, and Streptococcus pneumoniae to contact lenses (diclofenac) | >0.001 (31) | |||
| Reduction of adherence of Escherichia coli to silastic catheters | 0.28 (27), 0.14 (28) | |||||
| Reduction of adherence of Pseudomonas aeruginosa, Haemophilus influenzae, Staphylococcus epidermidis, and Streptococcus pneumoniae to contact lenses | >0.01 (31) | |||||
| Reduction of adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to human corneal epithelial cells | >0.01 (31) | |||||
| Biofilm production | Increase of biofilm production by Candida spp. | 0.015 (21) | Reduction of biofilm production by Candida spp. | 0.2b (21), 0.14 (32), 0.06b (33) | Increase of biofilm production by Candida spp. (ibuprofen) | 0.02 (21) |
| Reduction of biofilm production by Escherichia coli | 0.01 (35) | Reduction of biofilm production by Candida albicans (ibuprofen) | NS (32) | |||
| Reduction of biofilm production by Pseudomonas aeruginosa | 6b (37), 0.01 (39), 0.14 (38) | Disruption of mature biofilms in Candida albicans, Candida glabrata and Candida krusei (ibuprofen) | NS (16) | |||
| Reduction of biofilm production by Salmonella enterica serovar Typhimurium | NS (41) | |||||
| Reduction of biofilm production by Staphylococcus epidermidis | 0.69 (30, 40), 0.14 (38) | |||||
| Other virulence factors | Reduction of polysaccharide capsule production in Klebsiella pneumonia | 0.002 (6), 0.03 (43), 0.35 (44) | Reduction in hemolysin production in Escherichia coli (ibuprofen) | 0.004 (9) | ||
| Reduction of toxin production (hemolysin, elastase, protease, and pyocyanin) in Pseudomonas aeruginosa | 1b (37), 1.38 (39) | Decrease in urease activity in Helicobacter pylori (indomethacin) | 0.1 (45) | |||
| Reduction of membrane proteins and pathogenicity of Pseudomonas aeruginosa | 4.1 (112) | |||||
| Reduction of urease and vacuolating cytotoxin activity in Helicobacter pylori | 0.69b (5) | |||||
| Reduction of α-hemolysin production binding in Staphylococcus aureus | 0.03 (29) | |||||
| Reduction of teichoic acid, polysaccharide capsule and type 1 antigen production by Staphylococcus epidermidis | 0.69 (30) | |||||
| Metabolism | Downregulation of gluconeogenesis and glycolysis in Staphylococcus aureus | 0.69 (46) | Increase in expression of cytochrome P450 in Bacillus megaterium (ibuprofen/indomethacin) | NS (47, 113) | ||
| Activation of sugar transport (sorbitol, mannose) in Escherichia coli | 0.69 (46) | Metabolic alternation and damages of cytoplasmic membrane in Candida spp. (ibuprofen) | 3 (18) | |||
| Inhibition of transition from yeast to hyphae in Candida spp. (ibuprofen) | 0.1 (16) | |||||
| Interaction with immune system | Reduction in transport and release of azithromycin and moxifloxacin by PMNL | 0.005 (74) | Reduction in transport and release of azithromycin and moxifloxacin by PMNL | 0.005 (74) | Reduction in transport and release of azithromycin and moxifloxacin by PMNL (ibuprofen) | 0.005 (74) |
| Reduction in uptake of azithromycin by PMNL | 0.005 (74) | |||||
| Increase in phagocytosis of Klebsiella pneumonia by PMNL | 0.03 (43), 4 (86) | |||||
| Antibiotic susceptibility | Decrease in susceptibility of Serratia marcescens to cefotaxime, kanamycin | 0.005 (60) | Decrease in susceptibility of Escherichia coli to ofloxacin | 0.14 (93) | Increase in susceptibility of Helicobacter pylori to metronidazole and clarithromycin (indomethacin) | 0.04 (45) |
| Induction of β-lactamase activity in Serratia marcescens | 0.005 (60) | Increase in susceptibility of Acinetobacter baumannii to ceftriaxone, ciprofloxacin, gentamicin, imipenem | 0.35 (65) | Decrease in susceptibility of Bacillus pumilus, Escherichia coli, Salmonella Typhimurium, Shigella dysenteriae, Staphylococcus aureus and Vibrio cholerae to streptomycin (diclofenac) | 0.05 (92) | |
| Increase in susceptibility of Candida spp. to amphotericin B | NS (34) | Decrease in susceptibility of Burkholderia cepacia to chloramphenicol, ciprofloxacin, trimethoprim | 1.38 (48) | Increase in susceptibility of Candida spp. to azoles and amphotericin B (18, 71, 72) (ibuprofen) | 0.06 (18) | |
| Decrease in susceptibility of Campylobacter jejuni to chloramphenicol, ciprofloxacin, erythromycin, rifampin, tetracycline | 0.14 (49), 0.10 (50, 51) | Reversal of overexpression of efflux pumps in Candida spp. (ibuprofen) | 100 (72) | |||
| Decrease in susceptibility of Escherichia coli to ampicillin, cephalosporins, chloramphenicol, fluoroquinolones, nalidixic acid, tetracycline | 0.07 (55), 0.14 (52, 54), 0.69 (53, 87, 88) | |||||
| Increase in susceptibility of Escherichia coli to aminoglycosides | 0.28 (55) | |||||
| Increase in susceptibility of Helicobacter pylori to amoxicillin, clarithromycin, metronidazole | 1.38 (3, 69) | |||||
| Decrease in susceptibility of Klebsiella pneumonia to aztreonam, cefazolin, cefonicid, cefoperazone, ceftizoxime, clindamycin, doxycycline, mezlocillin, norfloxacin, trimethoprim-sulfamethoxazole | 0.35 (44) | |||||
| Increase in susceptibility of Klebsiella pneumonia amikacin, gentamicin, tobramycin | 0.35 (44, 68) | |||||
| Decrease in susceptibility of Pseudomonas aeruginosa to biapenem, carbenicillin, cefozopran, cefpirome, chloramphenicol, ciprofloxacin, gentamicin, imipenem, moxalactam, meropenem, norfloxacin, ofloxacin, panipenem, piperacillin | 0.14 (39), 0.55 (56), 4.4 (57) | |||||
| Increase in susceptibility of Pseudomonas aeruginosa to aztreonam, carbenicillin, cefotaxime, cefpiramide, chloramphenicol, piperacillin | 0.55 (56) | |||||
| Decrease in susceptibility of Pseudomonas aeruginosa to | 4.1 (112) | |||||
| Decrease in susceptibility of Salmonella enterica serovar Typhimurium to ampicillin, cefoperazone, chloramphenicol, ciprofloxacin, nalidixic acid, tetracycline | 0.69 (58), 0.35 (59) | |||||
| Decrease in susceptibility of Serratia marcescens to ampicillin, cefotaxime, cefoxitin, cephaloridine, ciprofloxacin, nalidixic acid, norfloxacin | 0.14 (60–62) | |||||
| Increase in susceptibility of Serratia marcescens to cephalothin, kanamycin | 0.41 (60) | |||||
| Decrease in susceptibility of Staphylococcus aureus to ciprofloxacin, norfloxacin, fusidic acid | 0.28 (64), 0.69 (63) | |||||
| Induction of β-lactamase activity in Serratia marcescens | 0.15 (60) | |||||
| Increase in susceptibility of Candida spp. to azoles and amphotericin B | 0.03 (34) | |||||
| Mutations | Suppression in the ability of metronidazole to induce mutations to rifampin in Helicobacter pylori | 0.10b (3) | ||||
| Increase (70-fold) in frequency of mutations leading to fluoroquinolone resistance in Campylobacter jejuni under selection with ciprofloxacin | 0.10 (50) | |||||
| Increase in mutations leading to fluoroquinolone resistance in Staphylococcus aureus | 0.28 (64, 73), 0.69 (63) | |||||
| Effects on viruses | Inhibition of hepatitis C virus cell entry (reduction in claudin-1 receptor) | 0.55b (75) | ||||
| Decrease in hepatitis C virus replication (modulation of inducible nitric oxide synthase and activation of p38 mitogen-activated protein kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2) | 0.55b (76, 77) | |||||
| Decrease of influenza virus replication (inhibition of nuclear factor-kappa B) | 0.14b (78) | |||||
| Decrease of flavivirus replication (activation of p38 mitogen-activated protein kinase) | 0.14 (79) | |||||
a
Concentrations at or below therapeutic plasma levels are indicated in bold. NS, not specified. PMNL, polymorphonuclear leukocytes.
b
Acetylsalicylic acid was used.